The proposed research includes 1) investigation of factors involved as determinants of rheologic properties and shape of normal erythrocytes, with particular emphasis on Ca ions accumulation, oxygen saturation, pH and hormone; 2) determination of the viscoelastic and failure characteristics of lipid-protein artificial membranes reconstituted from structural elements of human erythrocytes to determine the compounds and their interactions important to membrane physical properties; 3) definition of the abnormal structure and deformability characteristics of pathologic erythrocytes which may affect flow parameters in the microcirculation and 4) attempts to correlate oxygen delivery to specific tissues with capillary flow characteristics, erythrocyte membrane senescence and extrinsic parameters such as ambient pH. Studies will include separation of erythrocyte membrane proteins with characterization of divalent cation binding and calcium-induced protein conformational changes; characterization of Ca ions binding to inner surface of erythrocyte membranes as a function of ghost ATP and effects of binding on membrane ion permeability, deformability and distensibility; determination of cellular deformability and membrane viscoelastic properties by glass micropipettes; and observation of capillary flow in vivo by microscopic techniques coupled with videotape. Capillary intraluminal pressures will be monitored via micropipettes and transducers, and pH and pO2 will be measured by microelectrodes. Electron microscopy will be used to assist in characterization of membrane proteins and to define pathologic cell shape abnormalities.